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Ferrata Storti Foundation
Haematologica 2021 Volume 106(10):2694-2706
Carfilzomib or bortezomib in combination with cyclophosphamide and dexamethasone followed by carfilzomib maintenance for patients with multiple myeloma after one prior therapy: results from a multicenter, phase II, randomized, controlled trial (MUKfive)
Kwee L. Yong,1* Samantha Hinsley,2* Holger W. Auner,3 Ceri Bygrave,4 Martin F. Kaiser,5 Karthik Ramasamy,6 Ruth M. de Tute,7 Debbie Sherratt,2 Louise Flanagan,2 Mamta Garg,8 Stephen Hawkins,9 Catherine Williams,10 Jamie Cavenagh,11 Neil K. Rabin,12 James Croft,5 Gareth Morgan,13 Faith Davies,13 Roger G. Owen14 and Sarah R. Brown2
1Cancer Institute, University College London, London, UK; 2Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK; 3Department of Immunology and Inflammation and The Hugh and Josseline Langmuir Centre for Myeloma Research, Imperial College London, London, UK; 4Cardiff and Vale University Health Board, Cardiff, UK; 5The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, London, UK; 6Department of Clinical Haematology, Oxford University Hospitals NHS Trust, Oxford, UK; 7Department of Clinical Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, UK; 8Department of Haematology, University Hospitals of Leicester NHS Trust, Leicester, UK; 9The Clatterbridge Cancer Centre, Liverpool, UK; 10Centre for Clinical Haematology, Nottingham University Hospitals, Nottingham, UK; 11Department of Haematology, St Bartholomew's Hospital, London, UK; 12Department of Haematology, University College Hospital, London, UK; 13Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA and 14Haematological Malignancy Diagnostic Service (HMDS), St James's University Hospital, Leeds, UK
*KLY and SH contributed equally as co-first authors.
ABSTRACT
The proteasome inhibitors, carfilzomib and bortezomib, are widely used to treat myeloma but head-to-head comparisons have pro- duced conflicting results. We compared the activity of these protea- some inhibitors in combination with cyclophosphamide and dexametha- sone (KCd vs. VCd) in second-line treatment using fixed duration therapy and evaluated the efficacy of carfilzomib maintenance. MUKfive was a phase II controlled, parallel group trial that randomized patients (2:1) to KCd (n=201) or VCd (n=99); responding patients on carfilzomib were ran- domized to maintenance carfilzomib (n=69) or no further treatment (n=72). Primary endpoints were: (i) very good partial response (non-inferi- ority, odds ratio [OR] 0.8) at 24 weeks, and (ii) progression-free survival. More participants achieved a very good partial response or better with carfilzomib than with bortezomib (40.2% vs. 31.9%, OR=1.48, 90% con- fidence interval [CI]: 0.95, 2.31; non-inferior), with a trend for particular benefit in patients with adverse-risk disease. KCd was associated with higher overall response (partial response or better, 84.0% vs. 68.1%, OR=2.72, 90% CI: 1.62, 4.55, P=0.001). Neuropathy (grade ≥3 or ≥2 with pain) was more common with bortezomib (19.8% vs. 1.5%, P<0.0001), while grade ≥3 cardiac events and hypertension were only reported in the KCd arm (3.6% each). The median progression-free survival in the KCd arm was 11.7 months vs. 10.2 months in the VCd arm (hazard ratio [HR]=0.95, 80% CI: 0.77, 1.18). Carfilzomib maintenance was associated with longer progression-free survival, median 11.9 months vs. 5.6 months for no maintenance (HR 0.59, 80% CI: 0.46-0.77, P=0.0086). When used as fixed duration therapy in first relapase, KCd is at least as effective as VCd, and carfilzomib is an effective maintenance agent. This trial was registered with International Standard Randomised Controlled Trial Number (ISRCTN) identifier: ISRCTN17354232.
Plasma Cell Disorders
Correspondence:
KWEE L YONG
kwee.yong@ucl.ac.uk
Received: January 25, 2021. Accepted: April 14, 2021. Pre-published: April 29, 2021.
https://doi.org/10.3324/haematol.2021.278399 ©2021 Ferrata Storti Foundation
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